Nov 25, 2019

Lin28a/let-7 Pathway Modulates the Hox Code via Polycomb Regulation during Axial Patterning in Vertebrates

BioRxiv : the Preprint Server for Biology
Tempei SatoHiroshi Asahara

Abstract

The body plan along the anteroposterior axis and regional identities are specified by the spatiotemporal expression of Hox genes. Multistep controls are required for their unique expression patterns; however, the molecular mechanisms behind the tight control of Hox genes are not fully understood. In this study, we demonstrated that the Lin28a/let-7 reciprocal regulatory pathway is critical for vertebral specification. Lin28a-/- mice exhibited homeotic transformations of vertebrae which were caused by the global dysregulation of posterior Hox genes. The accumulation of let-7-family microRNAs in Lin28a-/- mice resulted in the reduction of PRC1 occupancy at the Hox cluster loci by targeting Cbx2. Consistently, Lin28a loss in embryonic stem-like cells led to aberrant induction of posterior Hox genes, which was rescued by the knockdown of let-7-family microRNAs. These results suggest that Lin28/let-7 pathway is possibly involved in the modulation of the 'Hox code' via Polycomb regulation during axial patterning in vertebrates.

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Mentioned in this Paper

Vertebrates
Study
Biochemical Pathway
Plasmodium sp. LIN28A
Patterns
Gene Knockdown Techniques
Regulation of Biological Process
Axial
Lin28A protein, human
MIRLET7I

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